Globular adiponectin inhibits angiotensin II-induced nuclear factor κB activation through AMP-activated protein kinase in cardiac hypertrophy

✍ Scribed by Cheng Wang; Li Li; Zhi-Guo Zhang; Dong Fan; Yi Zhu; Li-Ling Wu

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 241 KB
• Volume: 222
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21931

✦ Synopsis

Abstract

Activation of nuclear factor κB (NF‐κB) has been found necessary for cardiac hypertrophic growth in vivo and in vitro experiments. Adiponectin, an adipocyte‐derived polypeptide, suppresses cardiac hypertrophy in response to pressure overload. Here we investigated the potential effect of adiponectin on NF‐κB activation in hypertrophic neonatal rat ventricular myocytes (NRVMs) and related signal transduction pathway. We treated NRVMs with globular adiponectin (gAd) before angiotensin II (AngII) stimulation. Pretreating cells with gAd reduced the increased incorporation of [^3^H]‐leucine and the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulated by AngII, indicating gAd inhibited AngII‐induced cardiac hypertrophic signaling. Moreover, gAd pretreatment suppressed inhibitory protein κB (I‐κB) phosphorylation and decreased p65 nuclear translocation, DNA‐binding and transcription activity of NF‐κB. Meanwhile, gAd promoted AMP‐activated protein kinase (AMPK) phosphorylation, which is a downstream signaling mediator of adiponectin. Pharmacological activator of AMPK could inhibit AngII‐induced NF‐κB translocation, and inhibitor of AMPK or a dominant‐negative AMPK adenovirus suppressed gAd‐mediated inhibition of I‐κB phosphorylation and NF‐κB activation. When AMPK was inhibited, the suppressive effect of gAd on ANP mRNA expression was reduced. Our data indicate that gAd inhibits cardiac hypertrophic signaling through AMPK mediated suppression of NF‐κB activation. J. Cell. Physiol. 222:149–155, 2010. © 2009 Wiley‐Liss, Inc.